Survivin is a novel member of the inhibitor of apoptosis (IAP) protein family (1, 2). Different from other IAP members, survivin expression is undetectable in normal, differentiated adult tissues but is highly expressed in all common human cancers (1). Many important gene products including kinase and phosphatase molecules, transcription factors and other ligands or signaling molecules appear to exert their functions in various human pathological conditions (3) including cancer (2, 4), through the modulation of survivin expression (5). Survivin expression has been shown to be associated with tumorigenesis (4), cancer progression, poor disease outcome, shorter patient survival and drug/radiation resistance (1, 2). More importantly, survivin also appears to be required for angiogenesis, e.g. endothelial cell proliferation and migration (1). Thus, inhibition of survivin will not only directly induce apoptosis but also will block angiogenesis during tumor progression. Intriguingly, the gene regulation and the functional mechanism for survivin in cancer appear to be different from that in the rare survivin-positive normal tissues or cells (3, 5). Thus, targeting survivin for cancer therapeutics would produce minimal toxicity to normal human tissues and organs. These observations make survivin not only an exciting novel molecular target for cancer treatment but also a universal biomarker and target for drug discovery and development.
While survivin is a validated ideal target for cancer treatment, survivin is also, however, a multifunctional molecule with multiple unique subcellular localizations. For example, survivin has been shown to associate with both mitotic spindles (6) and centromeres (7, 8) during mitosis (1) as well as on mitochondria (9). Its expression is involved in both the inhibition of apoptosis (6, 9) and the regulation of mitotic cell division (7, 8, 10, 11). Moreover, recent studies on survivin reveal emerging new roles for survivin in the promotion of G1/S transition (3) and the regulation of gene transcription (5). For example, survivin plays a critical role in the mediation of vitamin D3 (VD3) compound-induced cancer cell growth inhibition (G0/G1 arrest) and apoptosis induction (12). Therefore, the multiple functions and subcellular localizations of survivin raise concerns as to whether it will be possible to find a tractable and effective way to inhibit its multiple functions for cancer treatment. Thus, there is an ongoing need to develop tools for identifying agents that can affect survivin expression.